1. Field of the Invention
The present invention relates to methods for improving the accuracy and precision of data obtained from analytical procedures. In particular, the invention relates to compositions and methods of measuring levels of chemical noise and/or chemical cross talk induced in a test sample being analyzed with a biodetector.
2. Description of the Prior Art
"Chemical noise" is a term of art which suggests the presence of unwanted chemicals generated through means such as isotopic scrambling which interfere with the detection of a substance or chemical of interest from a sample. Chemical noise arises from naturally-occurring chemicals found in samples that are being analyzed. Lead, cyanide, DDT, PCB's, and the like occur in practically everything if one looks at a sample on a molecule-by-molecule basis. This naturally-occurring chemical background material can interfere with the accurate analysis of samples, especially when it is necessary to detect and identify the presence of minute quantities of an agent in a sample. Samples can also pick up chemicals from the background and introduce "noise" during analytical procedures. For example, if the amount of chemical noise is significant, the results obtained from analyzing a given sample can be skewed by orders of magnitude and provide one with false positive and/or false negative results.
An example of chemical cross-talk is illustrated below. A certain chemical reaction may involve methane (CH.sub.4). If one were to replace the hydrogen with deuterium and the carbon with carbon-13, the chemical formula would be .sup.13 C.sup.2 H.sub.4, for labeled methane. However, if one were to then mix the unlabeled methane with the labeled methane in a reaction vessel and later did an analysis, the following products might be found: ##STR1## With the labeled methane, one can determine that this type of atomic exchange was occurring. More importantly, one could determine that there was chemical noise or cross-talk involved in the reaction being monitored and measure it.
In view of this phenomenon, it becomes important, especially when accurate readings of samples are required, that biodetectors include some indication or measure of the magnitude of chemical noise and/or chemical cross-talk present in a sample during analysis in a biodetector detection system.
Recently, the military has adopted techniques where biodetectors are used to determine the presence of biological warfare materials in a sample. Given the highly lethal nature of such materials, accurate measurements are essential. Interference caused by chemical noise could cause military personnel to be unnecessarily exposed to hazardous materials or take unnecessary precautions. Thus, the biodetectors employed must be able to account for any chemical noise and/or cross-talk which would skew the analysis results.
Mass Spectrometry (MS) has long been used to study simple organic compounds. Peptides, proteins, and other biomolecules were often more difficult to analyze with MS. The molecules were simply too big and fragile to survive the high temperatures required to get samples into the gas phase for MS analysis. This problem, however, has been recently solved by the introduction of desorption techniques such as fast atom bombardment, Electrospray Ionization (ESI) and Matrix-Assisted Laser Desorption/Ionization (MALDI). Thus, mass spectrometry is now being used as an analytical procedure in biodetection applications.
Mass spectrometry can also be used to efficiently determine isotope ratios (the concentration of rare isotope to the concentration of total element) as low as one part per billion (ppb) in microgram to nanogram samples. Contamination of a sample with an isotope or otherwise unwanted chemical can occur during sample preparation and during the analytical methods used to analyze the sample. The isotope can be incorporated in the sample from the surrounding matrix (the environment at large) or due to radiation or other in situ production.
Isotopic labeling of chemicals has been traditionally used in mass spectrometry to profile reaction mechanisms. However, most studies have been limited to compounds of relatively low molecular weight. (See above reaction scheme concerning methane). For very large and/or complex mixtures, chemical exchange of labeled nuclei might occur which would, of course, limit the usefulness or value of the data obtained.